We are interested in the factors responsible for the exquisite bronchial sensitivity of patients with bronchial asthma to certain mediators. This is a continuation of a population, genetic family study of certain host factors in bronchial asthma. This study deals with factors that are involved in determining the natural history of bronchial asthma in the general population. One of the major questions in this study is whether the bronchial sensitivity of asthmatic individuals to methacholine occurs at an early age even before clinical manifestation of the disease occurs. We intend to use the methacholine inhalation challenge test as a means of defining asthma and possibly using this as a marker for elucidation of its genetic characteristics. Another major part of this study is to determine whether asthma is acquired, genetically transmitted, and/or the result of interaction of environmental and host factors. We intend to study the natural history of asthma and methacholine sensitivity in patients who currently have asthma, former asthmatics, their atopic and non-atopic siblings, concordant and discordant twin pairs and in persons in asthmatic families with alpha-1-antitrypsin phenotypes MS, MZ and MM. We will study the genetic characteristics of predisposition to asthma, in the above high risk groups as well as low risk groups such as non-atopic families. Parameters to be assessed include methacholine tolerance, allergy history and skin tests, serum IgE, protease inhibitor (Pi) types, and Histocompatability antigens.